Although depression increases the risk of cardiovascular (CVD) events independent of traditional risk factors, the underlying pathophysiologic mechanisms are poorly understood. Cellular aging has been proposed as a novel putative mechanism in the development of CVD events. Shorter leukocyte telomere length, a marker of cellular aging, is associated with the presence of CVD, and may also predict CVD events. Recent evidence suggests that psychological stress and depression are associated with shorter leukocyte telomere length, suggesting that cellular aging may be a novel mechanism that explains the relation between depression and incident CVD events. However, the exact relations between these risk markers (depression and telomere length) and incident CVD events remain unknown. Investigation into these relations has important implications for understanding how, at the cellular level, depression may promote the earlier onset of age-related diseases such CVD. Specific Aims: To determine the relations among depression, cellular aging, and incident CVD events, and to secondarily determine the independent contributions of depression and cellular aging to the risk for incident CVD events. Methods: A population-based prospective study (1995 Nova Scotia Health Survey, NSHS95) was conducted over 10 years ago, in which participants were randomly selected from the socialized medical registry, which included all citizens. Traditional CVD risk factors were obtained at baseline. Depressive symptoms, assessed by the Center for Epidemiological Studies Depression scale, were also obtained at baseline. Buffy coat samples were obtained from participants and maintained in a -80 degree C freezer. Participants gave permission for their medical registry records to be linked to their survey data, so that objectively documented previous and subsequent CVD events could be detected. We propose to assay the buffy coat samples for leukocyte telomere length to determine the relations among depression, telomere length and 10-year incident CVD events in NSHS95. We will also determine whether these relations are independent of traditional CVD risk factors, and also body mass index, inflammatory biomarkers (C-reactive protein, interleukin-6, &soluble intercellular adhesion molecule-1), physical activity, other medical co-morbidities, use of cardiovascular medications, &antidepressant medication use. This study will provide enhanced understanding into how depression increases the risk of incident CVD events, and may suggest ways to develop more effective preventive and treatment strategies. PUBLIC HEALTH RELEVANCE: Depression increases the risk of cardiovascular disease. The reasons for this relation are not well known. This study will help determine why depression increases the risk of cardiovascular disease and may suggest ways to develop more effective preventive and treatment strategies.